Prolonged Upright Posture Induces Calcified Hypertrophy in the Cartilage End Plate in Rat Lumbar Spine

Bian, Qin; Qian, Liang; Wan, Chao; Hou, Wei; Li, Chen Guang; Zhao, Yuechao; Lü, Sheng; Shi, Qi; Wang, Yong Jun

doi:10.1097/brs.0b013e3181ffde92

Cited by 19 publications

(15 citation statements)

References 25 publications

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“…We have previously found that excess activation of TGFβ causes sclerosis and angiogenesis of subchondral bone in the knee joint, which alters loading distribution on articular cartilage and is key in the pathogenesis of osteoarthritis (OA) 7 8 . Upregulation of TGFβ has been observed in calcified hypertrophic EPs of degenerative IVD 9 . Whether TGFβ is involved in EP sclerotic changes is unknown.…”

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confidence: 99%

Excessive Activation of TGFβ by Spinal Instability Causes Vertebral Endplate Sclerosis

Bian

Jain

et al. 2016

Sci Rep

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Narrowed intervertebral disc (IVD) space is a characteristic of IVD degeneration. EP sclerosis is associated with IVD, however the pathogenesis of EP hypertrophy is poorly understood. Here, we employed two spine instability mouse models to investigate temporal and spatial EP changes associated with IVD volume, considering them as a functional unit. We found that aberrant mechanical loading leads to accelerated ossification and hypertrophy of EP, decreased IVD volume and increased activation of TGFβ. Overexpression of active TGFβ in CED mice showed a similar phenotype of spine instability model. Administration of TGFβ Receptor I inhibitor attenuates pathologic changes of EP and prevents IVD narrowing. The aberrant activation of TGFβ resulting in EPs hypertrophy-induced IVD space narrowing provides a pharmacologic target that could have therapeutic potential to delay DDD.Degenerative disc disease (DDD) is one of the most common musculoskeletal disorders that is associated with disability and absenteeism from work. Degeneration has been detected as early as teenage years and severe degeneration is found in 60% of 70-year olds 1,2 . DDD typically presents with back pain and imposes an enormous socio-economic burden, over $100 billion annually in the US alone. This cost exceeds the combined costs of stroke, respiratory infection, diabetes, coronary artery disease and rheumatoid disease 1,2 . Several factors have been implicated to cause DDD such as aging, genetic predisposition, toxic factors, metabolic disorders, low-grade infection, neurogenic inflammation and mechanical factors 3 . However, the pathogenesis of DDD under mechanical loading environment is not well known.Intervertebral disc (IVD) is composed of three parts: gel-like nucleus pulposus (NP) in the central compartment surrounded by an annulus fibrosis (AF) ring, and both cranial and caudal cartilage endplates (EPs) that attach the IVD inner ring to the adjacent vertebrae. EPs transmit mechanical loads produced by body weight and muscle activity between the bony vertebrae and soft tissue 4 . Moreover, EPs serve as a selective permeability barrier, allowing passage of small solutes, such as nutrient substances but impeding transport of larger solutes such as inflammatory factors 5 . Sclerosis of EPs change the mechanical property and impair diffusion and nutrient supply, thus accelerating IVD degeneration 5 . However, the originating mechanism of EP pathology is still not clearly understood.EPs undergo calcification and ossification and become sclerotic with aging 6 . We have previously found that excess activation of TGFβ causes sclerosis and angiogenesis of subchondral bone in the knee joint, which alters loading distribution on articular cartilage and is key in the pathogenesis of osteoarthritis (OA) 7,8 . Upregulation of TGFβ has been observed in calcified hypertrophic EPs of degenerative IVD 9 . Whether TGFβ is involved in EP sclerotic changes is unknown.In this study, we investigated temporal and spatial EP changes resulting from mechanical stress by...

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confidence: 99%

Excessive Activation of TGFβ by Spinal Instability Causes Vertebral Endplate Sclerosis

Bian

Jain

et al. 2016

Sci Rep

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“…E nd-plate calcification correlates with the process of vertebral disc degeneration, which can cause or promote the process of intervertebral disc disease 7,21 . Mechanical strain is one of the causes of calcification 13 . In this study, chondrocytes stained positively with AR-S at pH 4.2, showing that mechanical strain can induce calcification in endplate chondrocytes.…”

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confidence: 99%

“…Cell growth, differentiation and function can be influenced by appropriate mechanical strain stimulation; excessive mechanical stimulation can damage cell structure. Previous studies have shown that mechanical stress is associated with calcification of the lumbar spine cartilage endplate 13 , which could affect the metabolism and functioning of the disc, then accelerate the process of intervertebral disc degeneration 14 . For testing purposes, 1000 m is probably an appropriate degree of physiological strain, no more than 4000 m strain occurs during vigorous physiological activity in humans 15,16 .…”

Section: Introductionmentioning

confidence: 99%

Intermittent Cyclic Mechanical Tension‐induced Down‐regulation of Ectonucleotide Pyrophosphatase Phosphodiesterase 1 Gene Expression is Mainly Dependent on TGF‐β1 in End‐plate Chondrocytes

Wang

et al. 2013

Orthopaedic Surgery

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“…A series of changes in the disc have been observed with aging, such as endplate calcification and disc degeneration. 4 , 5 Abnormal endplate calcification is observed in a disc degeneration model of mechanical instability in the cervical or lumbar spine. We therefore speculate that changes in endplate calcification are related to mechanical stress.…”

Section: Introductionmentioning

confidence: 99%

“…TGF-β1 is also able to induce extracellular pyrophosphate (ePPi) up-regulation via TGF-β1-induced Ank gene expression. 4 , 7 …”

Section: Introductionmentioning

confidence: 99%

Investigating conversion of endplate chondrocytes induced by intermittent cyclic mechanical unconfined compression in three-dimensional cultures

Zhang

Zheng

et al. 2014

Eur J Histochem

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Mechanical stimulation is known to regulate the calcification of endplate chondrocytes. The Ank protein has a strong influence on anti-calcification by transports intracellular inorganic pyrophosphate (PPi) to the extracellular matrix. It is known that TGF-β1 is able to induce Ank gene expression and protect chondrocyte calcification. Intermittent cyclic mechanical tension (ICMT) could induce calcification of endplate chondrocytes by decrease the expression of Ank gene. In this study, we investigated the relation of intermittent cyclic mechanical unconfined compression (ICMC) and Ank gene expression. We found that ICMC decreased the Ank gene expression in the endplate chondrocytes, and there was an decreased in the TGF-β1 expression after ICMC stimulation. The Ank gene expression significantly increased when treated by transforming growth factor alpha 1 (TGF-β1) in a dose-dependent manner and decreased when treated by SB431542 (ALK inhibitor) in a dose-dependent manner. Our results implicate that ICMC-induced downregulation of Ank gene expression may be regulated by TGF-β1 in end-plate chondrocytes.

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Prolonged Upright Posture Induces Calcified Hypertrophy in the Cartilage End Plate in Rat Lumbar Spine

Abstract: Prolonged upright posture induces cartilage end plate calcification and hypertrophy in rat lumbar spine.

Cited by 19 publications

References 25 publications

Excessive Activation of TGFβ by Spinal Instability Causes Vertebral Endplate Sclerosis

Excessive Activation of TGFβ by Spinal Instability Causes Vertebral Endplate Sclerosis

Intermittent Cyclic Mechanical Tension‐induced Down‐regulation of Ectonucleotide Pyrophosphatase Phosphodiesterase 1 Gene Expression is Mainly Dependent on TGF‐β1 in End‐plate Chondrocytes

Investigating conversion of endplate chondrocytes induced by intermittent cyclic mechanical unconfined compression in three-dimensional cultures

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